Increasing antibacterial resistance in Gram-positive bacteria has presented a formidable treatment problem. The enterococci, although traditionally no virulent pathogens, have been shown, when associated with Vancomycin resistance, to have an attributable mortality of approximately 40%. Staphylococcus aureus, the traditional pathogen of postoperative wounds, has been resistant to Penicillin due to production of penicillinases. This resistance was overcome by the development of various penicillinase stable β-lactams. But the pathogen responded by synthesizing modified target penicillin binding protein-2′ leading to less affinity for β-lactam antibiotics and a phenotype known as Methicillin Resistant S. aureus (MRSA). These strains, until recently were susceptible to Vancomycin, which in spite of its various drawbacks, has become the drug of choice for MRSA infections. Streptococcus pneumoniae is a major pathogen causing pneumonia, sinusitis and meningitis. Until very recently it was highly susceptible to penicillin. Recently though, different PBP 2′ strains with different susceptibility to penicillin have been reported from across the globe. Oxazolidinones are a new class of synthetic antimicrobial agents, which kill gram-positive pathogens by inhibiting a very early stage of protein synthesis. Oxazolidinones inhibit the formation of ribosomal initiation complex involving 30S and 50S ribosomes leading to prevention of initiation complex formation. Due to their novel mechanism of action, these compounds are active against pathogens resistant to other clinically useful antibiotics.
Various oxazolidinone derivatives have been disclosed and reportedly having antibacterial activity. However in view of the above, there remains a need for novel substituted phenyloxazolidinones, which in particular can be effective antibacterial agents.